Project Summary / Abstract
Primary visual cortex (V1) processes visual information along parallel pathways and distributes the
results to high level cortical areas and subcortical targets. In mice, a species that lacks a strong, columnar
organization, neurons carrying information from different streams are spatially intermixed, but
nevertheless connect with specificity, both within and across areas. How are connections between
neurons established on such a fine scale despite the spatial intermixing of neurons?
We hypothesize that the visual properties of receptive fields of V1 neurons correlate with transcriptomic
cell types, which further guide their projection patterns and orchestrate the wiring of local connections.
We will establish if there is a correlation between cell type and visual function in V1. Our strategy consists
of the following steps. Step 1) Express GCaMP8 in a sparse set of L2/3 neurons under the control of
tamoxifen. Step 2) Use volumetric, in-vivo 2-photon calcium imaging to extensively characterize the visual
properties of the labeled neurons. Step 3) Process the tissue using expansion-assisted iterative FISH
(EASI-FISH) to yield the transcriptomic signatures of cells within the volume. Importantly, we will
determine which cells express GCaMP8 that will provide the landmarks for alignment. Step 4) Alignment
between in-vivo recordings and transcriptomic data using GCaMP6 expression. Step 5) Clustering of
neurons according to visual properties and transcriptomic signature.
The project addresses one of NEI’s priorities: to improve the understanding of neural activity and
molecular events in the formation of central visual circuits. Success in this project will deliver the first
database of excitatory cells in L2/3 of the mouse containing a characterization of their visual properties,
cortical location, and transcriptomic signatures. We will test if basic properties of visual neurons, such as
their receptive field linearity, correlate with cell types. The work will pave the way to study critical
questions about how early visual experience interacts with genetic programs that lead to cell
differentiation and their connectivity in a future R01.